Circadian rhythms in inflammatory bowel disease: from physiological basis to chronotherapy applications

Inflammatory bowel disease (IBD), encompassing Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic and recurrent gastrointestinal inflammatory disorder. It is characterized by persistent mucosal inflammation, damage to the intestinal epithelium, and impaired tissue repair. The primary clinical symptoms of IBD include abdominal pain, diarrhea, and bloody stools, with the frequency and severity of episodes often exhibiting a distinct circadian rhythm pattern. Various studies have proven that circadian rhythm disorders (CRD) are implicated in the pathogenesis, exacerbation, and treatment outcomes of IBD. This connection arises from the crucial role that circadian and biological clock molecules play an important role in regulating the diversity and colonization of gut microbiota, modulating mucosal barrier function through the expression of tight junction proteins, and exerting immunoregulatory effects via regulating immune cell activation, proliferation, and migration. However, disruptions to these rhythms often stem from modern lifestyle factors such as shift work, sleep deprivation, or irregular eating patterns. This leads to dysbiosis of the gut microbiota, increased intestinal permeability, and abnormal activation of the immune system, thereby inducing the onset of IBD or exacerbating its progression. IBD symptoms exhibit significant circadian rhythmic fluctuations. For example, disease activity, gut microbiota composition, intestinal mucosal barrier function, and inflammatory cytokine expression levels often exhibit diurnal patterns. Furthermore, drug metabolism and efficacy are also regulated by circadian rhythms, influencing the pharmacokinetic characteristics and pharmacodynamic performance of common IBD treatment regimens, such as glucocorticoids and immunomodulators. For instance, administering certain medications at specific times can enhance bioavailability and reduce toxicity. It suggests the potential feasibility of chronotherapy strategies. Accordingly, this review explores the application prospects of chronotherapy in the management of IBD, including multiple potential pathways that restores circadian synchrony and improve the intestinal microenvironment. These include: timed medication administration that is based on chronopharmacology and disease activity fluctuations, time-restricted eating that means consuming meals within a prescribed window during active phases, and behavioral interventions like adequate light exposure and sleep. These approaches aim not only to enhance therapeutic efficacy, but also to mitigate drug side effects and improve the quality of life for patients, particularly IBD patients with sleep disturbances. In summary, integrating circadian biology into IBD research offers new insights into disease mechanisms and paves the way for personalized time-based therapeutic interventions. Future efforts should further advance clinical translational studies to identify optimal time windows and individualized treatment strategies for different IBD subtypes. This review synthesizes existing evidence to establish a foundational framework for future clinical research, emphasizing the critical importance of considering circadian rhythms in IBD management and treatment.